Top | Research | Members | Publications | History |Contact/Access

Development of Organ Design Technologies

In order for organs to function, it is important that cells and extracellular matrices take appropriate spatial coordination and construct microstructures. In the Regenerative Biology Laboratory, we are developping technologies to design the internal microstructures of so-called "cell aggregates" such as multicellular spheroids and organoids, and investigating what kind of fine structures are necessary for organ functions. Creating organs with various designs using cells or extracellular matrices as a building unit leads to not only understanding of the mechanisms to exert organ functions but also proposal of methods to controll organ functions. There is a possibility to be found new designs of organs suitable for in vitro pharmacokinetic studies or having high engraftment ratio in transplantation. Until now, human beings have developed various manufacturing industries by designing of woods, stones, metals and so on. The findings revealed in our laboratory have a potential to raise unprecedented manufacturing industry by designing of organs.

(1) Construction of liver-like tissues with microstructures
The formation of hepatic multicellular spheroids that agglutinate hepatocytes is generally well-known as a method to enhance liver functions. However, disorderly aggregation of hepatocytes results in various stresses on the cells. This is because hepatocyte is one of a epithelial cell. We, therefore, developed a method of three-dimentional culture for hepatocytes. It can load various amount of extracellular matrix into the multicellular spheroid. This method can also create a sinuloid-like spaces inside of the spheroids by preparing hydrogel beads with the same size as cells and aggregated them together with hepatocytes. Besides, effective colulture with non-parenchymal cells is avairable. These methods can be used in combination as necessary. Hepatic multicellular spheroids formed by these methods are considered to exert liver functions which cannot be detected by conventional methods. We are developing highly functional miniature liver devices in combination with other technologies like microfluidic devices.
How to make highly functional hepatic spheroids

(2) Construction of highly functional islet-like tissues
Pancreatic beta cells are known to have higher insulin secretion activity when forming cell aggregates in three dimensions than in two dimentional cultures. We confirmed that pancreatic alpha cells move spontaneously to the outside of pancreatic beta cells when they are mixed and formed into multicellular spheroids, and insulin secretion activity was improved by adequate rate of alpha cells. In this system, we found that sugar chains present on the surface of pancreatic β cells are involved in such spontaneous cell migration. In addition, sugar chain-dependent cell migration thought to be important for insulin secretion activity. These information would be indespensable to form "optimized islet" for transplantation using not only primary islet cells but iPS cell derived beta cells.
Design of highly functional islet-like tissue

(3) Construction of bone marrow-like tissues with hematopoietic niche
Bone marrow is a jelly like tissue in the bone and is an important organ for hematopoiesis. A microenvironment called hematopoietic niche is existed in it, and the elucidation of its substance is underway. We aim to form such hematopoietic niche in a reconstructive approach, and we are established a method to aggregate almost whole population of bone marrow cells and culture them as a bone marrow-like tissue in vitro.
Spheroid formation with bone marrow-derived cells

(4) Preparation of cell aggregates using various cells
In addition to the above cells, we are working on culturing cell aggregates with various cell types. We are actively working on collaborative research, so please feel free to contact us if you have any trouble in aggregation and culture of cells.

Top | Research | Members | Publications | History |Contact/Access